Our group has been working on the regulation of central metabolism in mycobacteria, a critical process for Mycobacterium tuberculosis to switch between active growth and dormancy. In collaboration with the teams of Roland Brosch (Institut Pasteur), Helen O’Hare (University of Leicester) and Riccardo Manganelli (University of Padua, Italy), we are focusing on the α-ketoglurate metabolic ‘crossroad’ between carbon and nitrogen metabolism. This key intermediate can be either substrate for the synthesis of glutamate (and then glutamine) via the glutamate dehydrogenase/glutamate synthase network, or can rather be converted, via the Krebs cycle, to succinyl-CoA through the action of the KDH complex (α-ketoglutarate dehydrogenase). We are now mostly working on the structural characterization of a mixed hybrid ‘supercomplex’ between KDH and the related complex of the pyruvate dehydrogenase (PDH), supposedly present in mycobacteria (and possibly the whole Actinobacteria phylum). More details in the relative project page.
Acyl-CoAs are the major metabolic carriers of carbon in living organisms. The most conserved ways to their synthesis include the oxidative decarboxylation of α-ketoacids carried out by three distinct enzymatic machineries: the pyruvate dehydrogenase […]
2015Thiophenecarboxamide Derivatives Activated by EthA Kill Mycobacterium tuberculosis by Inhibiting the CTP Synthetase PyrG, Chem. Biol. 2015 Jul;22(7):917-27.
2013GarA is an essential regulator of metabolism in Mycobacterium tuberculosis, Mol. Microbiol. 2013 Oct;90(2):356-66.
2008Regulation of glutamate metabolism by protein kinases in mycobacteria, Mol. Microbiol. 2008 Dec;70(6):1408-23.
2015The crystal structure of the catalytic domain of the ser/thr kinase PknA from M. tuberculosis shows an Src-like autoinhibited conformation, Proteins 2015 May;83(5):982-8.
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